| Project/Area Number |
16390208
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kagoshima University (2005-2006)
Kobe University (2004) |
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Principal Investigator |
INUI Akio Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院医歯学総合研究科, 教授 (80168418)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMIYA Mineko Shiga University of Medical Science, Associate Professor, 医学部, 助教授 (10199359)
OHHINATA Kohsaku Kyoto University, Graduate School of Agriculture, Assistant Professor, 大学院農学研究科, 講師 (00361147)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | cancer anorexia・cachexia / feeding regulatory peptides / ghrelin / gastrointestinal motility / integrative medicine / transgenic mice / translational research / 癌 / 栄養学 / アシルグレリン / デスアシルグレリン / 食欲・体重調節 / 胃十二指腸運動 / オベスタチン / 悪液質モデル / 視床下部 / 摂食行動 / 合成ペプチド |
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| Research Abstract |
Cachexia is among the most debilitating and life-threatening aspects of cancer and is associated with anorexia, fat and muscle tissue wasting, psychological distress, and a lower quality of life. Cachexia results from a failure of the adaptive feeding response seen in simple starvation and includes cytokine production. We demonstrated that cytokines play a pivotal role in long-term inhibition of feeding by mimicking the hypothalamic effect of excessive negative feedback signaling from leptin, a hormone secreted by adipose tissue, which is an integral component of the homeostatic loop of body weight regulation. The cytokine signaling leads to persistent inhibition of feeding-stimulatory circuitry including ghrelin-neuropeptide Y, as shown in our studies in colon26 or other cancer cell-bearing mice. The two major options for pharmacological therapy have been either progestational agents or corticosteroids. However, knowledge of the mechanisms of cancer anorexia-cachexia syndrome continue
… More
s to lead to effective therapeutic interventions for several aspects of the syndrome. We have shown that ghrelin agonist GHRP2 reverses anorexia induced by 5FU and increases cumulative food intake in cancer cachexia models. GHRP2 increases appetite in patients with depression. In contrast, desacyl ghrelin and obestatin, the another ghrelin gene products are anorexigenic and anti-gastroprokinetic as opposed to acyl ghrelin, and overproduction of the transgenic mice showed lean phenotype. Therfore, the relative abundance of these three ghrelin gene products may determine the overall output of the peptide system. Although we could not succeed to develop new peptides with increased potency compared to GHRP2, recent administration of ghrelin to anorexic patiens suggests the usefulness in improving anorexia. Because weight loss shortens the survival time of cancer patients and decreases performance status, effective therapy would extend patient survival and improve quality of life. Our animal experiments partly supported the notion. Less
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